AbstractFor optimization of liquid chromatography separations, several approaches have been reported, among them the use of the hydrophobic fragmental constant, as proposed by Rekker [1]. The fragmental constant is derived from the partition coefficients of various solutes between octanol and water and represents a summation of solubility parameters: van der Waals volume, π ‐ π interactions, hydrogen bonding, etc. With these constants the optimization of reversed phase mode liquid chromatography using octadecyl bonded silica gels as packing was feasible, although large error was found for the eluent with a high concentration of organic modifier or water. This is probably due to the heterogeneous solvation of the surface of the packings and to various solvent effects. In addition, when the acid dissociation constant was known, the retention times of aromatic acids in the ionic form were also predicted using the hydrophobic fragmental constant and the dissociation constant. By comparison of the previous data and a method proposed by Perrin et al. [2] it was possible to predict the dissociation constant of aromatic acids and optimize separation in reversed phase mode liquid chromatography using octadecyl bonded silica gels as packing. Furthermore, an equation for calculating the capacity ratios in a given pH eluent was proposed and the predicted and observed capacity ratios of aromatic acids in several eluents were examined in order to improve the above system.